Behavioural Correlates of Dopaminergic Agonists’ Dyskinetic Potential in the 6-OHDA-Lesioned Rat
Prolonged treatment with l-DOPA induces highly disabling dyskinesia in patients affected by Parkinson’s disease (PD). In contrast, dopamine receptor agonist treatments display dyskinetic outcome variably, depending on pharmacokinetic/pharmacodynamic drug profile. The present study was aimed at assessing behavioural correlates of intense or mild dyskinesia displayed by the different dopamine receptor stimulation in the 6-hydroxydopamine rat model of PD. Sensitization of contralateral turning behaviour (SCT) and abnormal involuntary movements (AIMs) were assessed as behavioural correlates of dyskinetic responses during subchronic stimulation of the D1 receptor by SKF38393 and the D2/D3 receptors by ropinirole. Similarly to what already has been described for l-DOPA, subchronic SKF38393 caused AIMs and SCT whereas ropinirole elicited SCT only, indicating that both drugs induced some dyskinetic response, albeit of different type. Results suggest that presence of SCT alone or SCT plus AIMs might represent correlates of the differential severity of dyskinetic movements induced by treatment with low (ropinirole) or high (SKF38393) dyskinetic potential. Evaluation of both behavioural responses represents a useful test to predict the dyskinetic potential of drugs in preclinical screening.
KeywordsBehavioural Correlate Dopaminergic Agonist Subchronic Treatment Contralateral Turning Agonist Ropinirole
The authors thank GlaxoSmithKline (Harlow, Essex, UK) for providing ropinirole. This work was supported by a grant from MURST – project FIRB (RBNE03YA3L-2005).
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